Process and intermediate compounds useful in the preparation of statins, particularly rosuvastatin

Abstract

Provided are a compound of formula (5) and a process for its preparation wherein: R 1 represents an alkyl group; R 2 represents an aryl group; R 3 represents a protecting group or an alkyl group; R 4 represents a protecting group or a SO 2 R 5 group where R 5 is an alkyl group; R 6 represents (PR 7 R 8 ) + X − or P(═O)R 7 R 8 in which X is an anion and R 7 and R 8 each independently is an alkyl, aryl, alkoxy, or aryloxy group; P 1 represents hydrogen or a protecting group; and W represents ═O or OP 2 , in which P 2 represents hydrogen or a protecting group.

The invention claimed is: 
     
       1. A process for the preparation of a compound of formula (5) 
       
         
           
           
               
               
           
         
         comprising coupling a compound of formula (3) 
       
       
         
           
           
               
               
           
         
         with a compound of formula (4) 
       
       
         
           
           
               
               
           
         
         wherein: 
         R 1  represents an alkyl group; 
         R 2  represents an aryl group; 
         R 3  represents a protecting group or an alkyl group; 
         R 4  represents a protecting group or a SO 2 R 5  group where R 5  is an alkyl group; 
         R 6  represents (PR 7 R 8 ) + X −  or P(═O)R 7 R 8  in which X is an anion and R 7  and R 8  each independently is an alkyl, aryl, alkoxy, or aryloxy group; 
         P 1  represents hydrogen or a protecting group; and 
         W represents —OP 2 , in which P 2  represents hydrogen or a protecting group. 
       
     
     
       2. A compound of formula (5) 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  represents an alkyl group; 
         R 2  represents an aryl group; 
         R 3  represents hydrogen, a protecting group, or an alkyl group; 
         R 4  represents a protecting group or a SO 2 R 5  group where R 5  is an alkyl group; 
         P 1  represents hydrogen or a protecting group; and 
         W represents —OP 2 , in which P 2  represents hydrogen or a protecting group. 
       
     
     
       3. The process of  claim 1 , wherein each of R 7  and R 8  is a phenyl group. 
     
     
       4. The process of  claim 1 , wherein R 1  represents a C 1-6  alkyl group. 
     
     
       5. The process of  claim 4 , wherein R 1  represents an isopropyl group. 
     
     
       6. The process of  claim 1 , wherein R 2  is 4-fluorophenyl group. 
     
     
       7. The process of  claim 1 , wherein R 3  represents a C 1-6  alkyl group. 
     
     
       8. The process of  claim 1 , wherein R 3  represents a methyl group. 
     
     
       9. The process of  claim 1 , wherein R 5  is a C 1-6  alkyl group. 
     
     
       10. The process of  claim 9 , wherein R 5  is a methyl group. 
     
     
       11. The process of  claim 1 , wherein P 1  represents hydrogen or a protecting group selected from the group consisting of tetrahydropyranyl, benzyl, methyl, silyl, and benzoyl. 
     
     
       12. The process of  claim 1 , wherein P 2  represents a protecting group selected from the group consisting of tetrahydropyranyl, benzyl, methyl, silyl, and benzoyl. 
     
     
       13. The compound of  claim 2 , wherein R 1  represents a C 1-6  alkyl group. 
     
     
       14. The compound of  claim 13 , wherein R 1  represents an isopropyl group. 
     
     
       15. The compound of  claim 2 , wherein R 2  is 4-fluorophenyl group. 
     
     
       16. The compound of  claim 2 , wherein R 3  represents a C 1-6  alkyl group. 
     
     
       17. The compound of  claim 2 , wherein R 3  represents a methyl group. 
     
     
       18. The compound of  claim 2 , wherein R 5  is a C 1-6  alkyl group. 
     
     
       19. The compound of  claim 18 , wherein R 5  is a methyl group. 
     
     
       20. The compound of  claim 2 , wherein P 1  represents hydrogen or a protecting group selected from the group consisting of tetrahydropyranyl, benzyl, methyl, silyl, and benzoyl. 
     
     
       21. The compound of  claim 2 , wherein P 2  represents a protecting group selected from the group consisting of tetrahydropyranyl, benzyl, methyl, silyl, and benzoyl.